Metabolic engineering for the production of clinically important molecules: Omega-3 fatty acids, artemisinin, and taxol

Graphical Abstract

Metabolic engineering harnesses the intrinsic metabolic machinery of cells for the manufacture of useful molecules. One approach for metabolic engineering is to tune existing biochemical pathways within cells to maximize synthesis of desired molecular entities. The review article describes the utility of metabolic engineering for producing three molecules that are important for the biomedical community: (A) omega-3 fatty acids, (B) artemisinin, and (C) taxol, in a variety of cellular hosts.

Abstract

Driven by requirements for sustainability as well as affordability and efficiency, metabolic engineering of plants and microorganisms is increasingly being pursued to produce compounds for clinical applications. This review discusses three such examples of the clinical relevance of metabolic engineering: the production of omega-3 fatty acids for the prevention of cardiovascular disease; the biosynthesis of artemisinic acid, an anti-malarial drug precursor, for the treatment of malaria; and the production of the complex natural molecule taxol, an anti-cancer agent. In terms of omega-3 fatty acids, bioengineering of fatty acid metabolism by expressing desaturases and elongases, both in soybeans and oleaginous yeast, has resulted in commercial-scale production of these beneficial molecules. Equal success has been achieved with the biosynthesis of artemisinic acid at low cost for developing countries. This is accomplished through channeling the flux of the isoprenoid pathway to the specific genes involved in artemisinin biosynthesis. Efficient coupling of the isoprenoid pathway also leads to the construction of an Escherichia coli strain that produces a high titer of taxadiene-the first committed intermediate for taxol biosynthesis. These examples of synthetic biology demonstrate the versatility of metabolic engineering to bring new solutions to our health needs.